Hematopathology Case Study: A 65 Year Old Male with a Skin Lesion on the Right Shoulder

Case History

A 65 year old Caucasian male presents with a skin lesion on his right shoulder. Physical examination reveals a 3 .0 cm × 1.5 cm hyperpigmented plaque with mild hyperkeratosis on his right shoulder and multiple scattered erythematous macules and plaques on the trunk and back Skin biopsy reveals involvement by Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN). PET scan reveals no extracutaneous involvement.

The patient undergoes CHOP
chemotherapy followed by autologous hematopoietic stem cell transplantation. He is subsequently treated
systemically with lanolidomide,
venetoclax, and idelalisib due to relapses of disease.

The patient returns to
clinic three years later for follow-up. While his original cutaneous lesions are
completely resolved, new lesions are noted on his back (representative lesion,
Image 1). Hematologic evaluation is remarkable for pancytopenia with hemoglobin
8.7gm/dL, white blood cells 1.4 K/uL, and platelets 39 K/uL. A biopsy of the
bone marrow is performed.

Image 1. Skin lesion on back.

Biopsy Findings

Core biopsyCD56Aspirate

H&E stained sections
demonstrate a normocellular bone marrow with diminished trilineage
hematopoiesis and sheets of amphophilic, blastoid cells with irregular borders
occupying most of the marrow cells. Immunohistochemistry demonstrates a cellular population with CD56. The aspirate smears show similar findings with numerous
clustered blastoid cells (92%) with a monocytoid appearance, often with
basophilic vacuolated cytoplasm. There is also a decrease in myeloid and
erythroid precursors.

Flow cytometric analysis
performed on the bone marrow aspirate reveals a dim CD45 population with
expression of CD4, CD56, partial CD7, dim and partial CD5, and CD38. The same population
lacks expression of immaturity markers such as CD34, MPO, and TdT. The
morphologic and phenotypic findings found in the marrow specimen are diagnostic
of extensive involvement of the marrow by BPDCN.

Discussion

BPDCN is a
rare and highly aggressive malignancy derived
from precursors of
plasmacytoid dendritic cells. Its nomenclature has constantly
changed over years as the understanding of this entity has been improved. It
has been variously known as blastic natural killer cell lymphoma/leukemia, agranular
CD4+ natural killer cell leukemia, and CD4+CD56+haematodermic neoplasm. It is currently classified under acute
myeloid leukemia and related precursor neoplasms in the most recent WHO
classification of tumours of haematopoietic and lymphoid organs.

Limited data exist regarding the incidence of
BPDCN; however, it is estimated to account for 0.7% of primary cutaneous skin
lymphomas and 0.44% of all hematological malignancies. This hematodermic malignancy predominantly
affects elderly male patients with mean age ranging from 60 to 70; however, a
few cases have also been reported in childhood and infancy. As demonstrated in
our case, the patients typically present with multiple
violaceous skin lesions, which may be associate with erythema,
hyperpigmentation, purpura, or ulceration. Extracutaneous involvement is
reported to occur in the bone marrow, peripheral blood, and lymph nodes.

The clinical course of BPDCN is aggressive, with
a median survival of 9 to 16 months. The patients with disease limited to the
skin may have a better prognosis, while advanced age and advanced clinical
stage are indicators of poor prognosis. There
is currently no consensus on optimal management and treatment because of low
incidence of BPDCN; however, most patients are treated with regimens used for other hematopoietic
malignancies (i.e. CHOP and hyperCVAD) followed by allogeneic stem cell
transplantation for eligible patients. They often respond well to chemotherapy
with complete resolution of skin lesions; however, relapse of disease can occur
due to resistance to chemotherapeutic agents, which may have happened in our
case.

-Jasmine Saleh, MD MPH is a pathology resident at Loyola University Medical Center with an interest in dermatopathology and hematopathology. Follow Dr. Saleh on Twitter @JasmineSaleh.

-Kamran M. Mirza, MD PhD is an Assistant Professor of Pathology and Medical Director of Molecular Pathology at Loyola University Medical Center. He was a top 5 honoree in ASCP’s Forty Under 40 2017. Follow Dr. Mirza on twitter @kmirza.